The form, structure and functional integrity of man and all higher animals is defined by the set of extracellular tissue elements known collectively as the connective tissues. The collagen fiber systems represent the major constituents of the connective tissues and, as the most ubiquitous components of all animals, pervade every tissue and organ. The collagen fibers have the majority of their features in common, but tissue specific differences at both the individual chemical structure level and at the fiber organization level have been described. The purpose of our investigations is to examine those factors which relate to the organization of the fibers, their stabilization, maintenance and degradation. The particular attack on these questions is at several levels: the biosynthesis of collagen in procollagen form; the heterogeneity of the collagen produced; the stages, in vivo, of the conversion of procollagen to collagen; the role of intermediates in this process in the formation of insoluble fibrils; and, the structures of the fibers themselves. Throughout these studies, tissue specificity will be considered as an important adjunct to structure-function relationships. We also intend to examine tissues in both the normal and disease state from patients with chronic connective tissue disorders. The coordination of the several individual projects attacking problems posed above in quite different ways provides a frame of reference giving coherence to the overall program.